Endocrine System
内分泌系统
Linlin Wang（王琳琳）
E-mail: Wanglinlin@zju.edu.cn
Endocrine System
‡One of the two major communication systems in
the body
¾ Have much longer delays
¾ Last for much greater lengths of time
‡Integrating stimuli and responses to changes in
external and internal environment
‡Crucial to coordinated functions of highly
differentiated cells, tissues and organs
‡ Endocrine Glands
¾ Hypothalamus
¾ Pituitary (Anterior and Posterior)
¾ Thyroid / Parathyroid
¾ Endocrine Pancreas (islets)
¾ Adrenal Cortex and Medulla
¾ Gonad (Ovary and Testis)
Endocrine gland
(ductless) is a group of
cells that produce and
secret a hormone
Endocrine cell
What is a hormone?
• Chemical messenger synthesized by specific
endocrine cells in response to certain stimuli and
secreted into the blood
• Travel via the circulation to affect one or more
groups of different cells (target cells) to elicit a
physiological response
Hormones are primarily information transferring
molecules
What is a hormone?
‡Definition
– Chemical messengers
– Secreted into blood or extracellular fluid
– Affecting the functions of other cells
‡Functions
– Regulation of metabolism, growth and
development, water and electrolyte balance,
reproduction, and behavior
• The endocrine system broadcasts
its hormonal messages to target
cells by secretion into blood and
extracellular fluid. Like a radio
broadcast, it requires a receiver to
get the message - in the case of
endocrine messages, cells must bear
a receptor for the hormone being
broadcast in order to respond.
Types of Hormones
‡Amines 胺类激素
– Thyroid hormones, E, NE
‡Proteins and polypeptides 多肽/蛋白质类激素
– Pituitary hormones, insulin and glucagon
‡Steroids 类固醇激素
– Sex hormones, cortisol and aldosterone
‡ 脂肪酸衍生物
– 前列腺素
Types of Hormones
Types
Amines
Steroids
Protein and
peptides
Example
T4, T3,
catecholamine
Hormones
from adrenal
cortex
and gonads
Most of hormones
insulin, oxytocin,
GH
Synthesis
Tyrosine
Cholesterol
DNA – mRNA –
Preprohormone Prohormone
Feature
lipid insoluble lipid soluble lipid insoluble
Synthesis of peptide hormones
DNA
前激素原
pre-pro-insulin
pro-insulin
insulin
Synthesis of steroid hormones
‡ From cholesterol
‡ Not stored
Hormone Storage and Release
‡Thyroid and steroid hormones
– Not stored as secretory granules
– Transferring through plasma membrane
‡Protein and catecholamine hormones
– Stored as secretory granules
– Released by exocytosis
Hormones are not secreted at a
uniform rate
‡ In a pulsatile pattern
脉动节律
‡ Diurnal (circadian) rhythm:24小时周期节律
– linked to sleep-wake cycles (cortisol, growth hormone)
„Be
aware of the pulsatile nature and
rhythmic pattern of hormone secretion when
relating the serum hormone measurements
to normal values
Modes of Action
‡Endocrine 内分泌 – transmission of a signal from a
classic endocrine cell through bloodstream to a
distant target cell
‡Neurocrine 神经分泌 – hormone is released from a
neuron down its axon and then travels via the
bloodstream to target cell
‡Paracrine 旁分泌 – hormone acts on adjacent cells
‡Autocrine 自分泌 – hormone is released and acts
on the cell that secreted it. e.g. norepinephrine
itself inhibits further release by that cell in the
adrenal medulla
Hormone Transport
‡Peptides and catecholamine
– water soluble
– dissolve in blood
– circulate in blood mainly in free form
‡Steroid and thyroid hormones
– circulate in blood mainly bound to plasma proteins
– the free form is biologically active
– the greater binding, the longer half-life
Hormone Clearance
‡The half-life of a hormone in blood
– Free: min
– Binding: mins, hrs, days
• e.g. T4 (6 days); Insulin (0.006 days)
‡Ways of Clearance
– target cell uptake
– metabolic degradation
– urinary or biliary excretion
The “metabolic fate” of a given
hormone molecule in the blood
Characteristics of Hormones
• Regulates rate of reaction
• Do not initiate
• Very specific
• Amplification effect
– Present in very small quantity
• pg/mL ~ μg/mL
Each protein kinase
can catalyse hundreds
of reactions
录像\Signal
amplification.swf
The cAMP system rapidly amplifies the response
capacity of cells: here, one “first messenger” led
to the formation of one million product molecules.
‡Interaction between hormones
• Synergistic action 协同作用
• Antagonistic action 拮抗作用
• Permissive action 允许作用
– Hormone A must be present for the full strength
of hormone B’s effect.
– Up-regulation of one hormone’s receptors by
another hormone
– the facilitation of the action of one hormone by
another
Regulation of Hormone
Secretion
Regulation of Hormone
Secretion
‡Negative feedback
– Most common
– Occurs when a hormone
produces a biologic effect
that, on attaining sufficient
magnitude, inhibits further
secretion
‡Positive feedback
– Less common
– Amplify the initial biological
effect of the hormone
Mechanisms of hormone actions
‡Hormone action mediated by the specific
receptors
– A target cell responds to a hormone because it
bears receptors for the hormone
‡Two general mechanisms of hormone
action
– Second messengers – enzyme activity ↑↓
(rapid, cytosolic effects)
– Gene expression - enzymes synthesis ↑↓
(slow, nuclear effects)
Mechanisms of Peptide
Hormone Action
‡ G proteins
–
–
–
–
–
–
–
are GTP-binding proteins
couple hormone receptors to adjacent effector molecule
have intrinsic GTPase activity
have three subunits: α, β, γ
α subunit bound to GDP → inactive G protein
α subunit bound to GTP → active G protein
the effect can be either stimulatory (Gs) or inhibitory (Gi)
‡ Second messengers
– cAMP second message system
– IP3 mechanism
– Ca2+-calmodulin mechanism
Signal transduction pathway involving
adenylate cyclase
录像\Membrane-bound receptors, G proteins, and Ca2+ channels.swf
PIP-calcium signaling mechanism
This receptor-G-protein complex is linked to and activates phospholipase C,
leading to an increase in IP3 and DAG, which work together to activate
enzymes and to increase intracellular calcium levels.
Ca-calmodulin
system
Mechanisms of steroid
Hormone Action
‡Modulation of gene expression
– Steroid hormones bind to intracellular receptors
– The steroid-receptor complex binds to DNA,
turning specific genes on or off
Steroid hormone receptor
Sequence of events for steroid
hormone binding
‡ Steroids are lipid-based and can diffuse into cells easily
‡ No need for intracellular second messenger
‡ Mobile receptors
– Some steroids bind to a cytoplasmic receptor, which then translocates
to the nucleus
– Other receptors for steroids are located in the nucleus or are nuclear
receptor proteins
– In both cases, the steroid-receptor complex formed can then bind to
specific regions of DNA and activate specific genes
‡ Activated genes transcribe into messenger RNA and
instruct the cell to synthesize specific enzyme proteins
that change the metabolism of the target cell录像\How
intracellular receptors regulate gene transcription.swf
Summary
• Terms
– Hormone激素
– Permissive action激素允许作用
Summary
• Hormone激素
– Primarily information transferring molecules
– Transfer information from one set of cells to another
– Travel via the circulation to affect one or more groups of different
cells to elicit a physiological response
• Hormone types激素类型
– Protein and peptides
– Amines
– Steroids
• Action modes of hormones激素作用方式
–
–
–
–
Endocrine
Paracrine
Autocrine
Neurocrine
Summary
• Regulation of Hormone Secretion激素分泌调节
– Negative feedback
– Positive feedback
• Mechanisms of hormone action激素作用机制
– Mechanisms of Peptide Hormone Action
• Second messenger signaling pathway
– cAMP second message system
– IP3 mechanism
– Ca2+-calmodulin mechanism
– Mechanisms of Steroid Hormone Action
• Modification of gene expression
General question
• What are the mechanisms of action
of peptide/protein hormones?
Recommended TEXTBOOK:
Widmaier EP, Raff H, Strang KT (2006) Vander’s Human Physiology:
The Mechanisms of Body Function, 12th Edition. McGraw-Hill.
Recommended WEBSITERS:
http://www.endocrineweb.com/
http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/index.html
http://medical.physiology.uab.edu/cardio.htm
http://www.mhhe.com/biosci/ap/foxhumphys/student/olc/index.htm